The present invention relates to medicaments comprising, as active principle, at least one compound of general formula: 
in their stereoisomeric forms or their salts with an inorganic or organic acid, to novel compounds of formula (I) or their salts with an inorganic or organic acid, and to their preparation.
In the general formula (I):
R1 represents the stereoisomeric forms of the chain
xe2x80x94(CHOH)3xe2x80x94CH2OH xe2x80x83xe2x80x83(II) 
and
either R2 represents a hydrogen atom and R3 represents the stereoisomeric forms of the chain
xe2x80x94CH2xe2x80x94(CHOH)2xe2x80x94CH2OH xe2x80x83xe2x80x83(III) 
or R2 represents the stereoisomeric forms of the chains
xe2x80x94(CHOH)3xe2x80x94CH2OH xe2x80x83xe2x80x83(II) 
or
xe2x80x94CH2xe2x80x94(CHOH)2xe2x80x94CH2OH xe2x80x83xe2x80x83(III) 
and R3 represents a hydrogen atom with the exception of
fructosazine of formula 
deoxyfructosazine of formula 
and the compound of formula 
The medicaments according to the invention thus comprise at least one stereoisomer of the following compounds: 
or a salt of such a compound with an organic or inorganic acid, with the exception of fructosazine, deoxyfructosazine and the compound of formula (VI).
The medicaments according to the invention are preferably those which comprise, as active principle, at least one compound of formula (I) chosen from the following compounds:
1-[5-(1R,2R,3R,4-tetrahydroxybutyl)pyrazin-2-yl]butane-1R,2R,3R,4-tetraol
1-[5-(1R,2R,3S,4-tetrahydroxybutyl)pyrazin-2-yl]butane-1R,2R,3S,4-tetraol
1-[5-(1R,2S,3S,4-tetrahydroxybutyl)pyrazin-2-yl]butane-1R,2S,3S,4-tetraol
1-[5-(1S,2R,3R,4-tetrahydroxybutyl)pyrazin-2-yl]butane-1S,2R,3R,4-tetraol
1-[5-(1S,2R,3S,4-tetrahydroxybutyl)pyrazin-2-yl]butane-1S,2R,3S,4-tetraol
1-[5-(1S,2S,3R,4-tetrahydroxybutyl)pyrazin-2-yl]butane-1S,2S,3R,4-tetraol
1-[5-(1S,2S,3S,4-tetrahydroxybutyl)pyrazin-2-yl]butane-1S,2S,3S,4-tetraol
1-[5-(2R,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1R,2R,3R,4-tetraol
1-[5-(2R,3S,4-trihydroxybutyl)pyrazin-2-yl]butane-1R,2R,3S,4-tetraol
1-[5-(2S,3S,4-trihydroxybutyl)pyrazin-2-yl]butane-1R,2S,3S,4-tetraol
1-[5-(2R,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2R,3R,4-tetraol
1-[5-(2R,3S,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2R,3S,4-tetraol
1-[5-(2S,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2S,3R,4-tetraol
1-[5-(2S,3S,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2S,3S,4-tetraol
1-[6-(2R,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1R,2R,3R,4-tetraol
1-[6-(2R,3S,4-trihydroxybutyl)pyrazin-2-yl]butane-1R,2R,3S,4-tetraol
1-[6-(2R,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2R,3R,4-tetraol
1-[6-(2R,3S,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2R,3S,4-tetraol
1-[6-(2S,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2S,3R,4-tetraol
1-[6-(2S,3S,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2S,3S,4-tetraol
or a salt of such a compound with an inorganic or organic acid,
and, more advantageously still, those which comprise, as active principle, at least one compound of formula (I) chosen from the following compounds:
1-[5-(1R,2R,3R,4-tetrahydroxybutyl)pyrazin-2-yl]butane-1R,2R,3R,4-tetraol
1-[5-(2R,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1R,2R,3R,4-tetraol
1-[5-(2S,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2S,3R,4-tetraol
1-[6-(2R,3S,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2R,3S,4-tetraol
1-[6-(2R,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1R,2R,3R,4-tetraol
or a salt of such a compound with an inorganic or organic acid.
The following compounds are known:
fructosazine, deoxyfructozasine and the compound of formula (VI) are described (Patent JP 43-13469, Ann., 644, 122-127 (1961); Agr. Biol. Chem., 39 (5), 1143-1148 (1975)),
the stereoisomers of general formula (VIa), (VIb), (VIc) and (VId) mentioned hereinbelow have been described (Patent JP 43-13469, Carbohyd. Res., 26(2), 377-84 (1973), J. Anal. Appl. Pyrolysis, 13, 191-198(1988)) 
the compounds of general formulae (VII), (VIII) and (IX) resulting from glucose, fructose, mannose and galactose have been described in Japanese Patent JP 53-90401.
However, their use as medicament has not been mentioned and this is the subject matter of the present invention.
The compounds of formula (I) or their salts with an inorganic or organic acid, with the exception of the following compounds: 
are novel and, as such, form part of the invention.
The preferred compounds of formula (I) are the following:
1-[5-(1R,2R,3S,4-tetrahydroxybutyl)pyrazin-2-yl]butane-1R,2R,3S,4-tetraol
1-[5-(1S, 2R, 3R, 4-tetrahydroxybutyl)pyrazin-2-yl]butane-1S,2R,3R,4-tetraol
1-[5-(1S,2S,3R,4-tetrahydroxybutyl)pyrazin-2-yl]butane-1S,2S,3R,4-tetraol
1-[5- (1S, 2S,3S, 4-tetrahydroxybutyl)pyrazin-2-yl butane-1S,2S,3S,4-tetraol
1-[5-(2R,3S,4-trihydroxybutyl)pyrazin-2-yl]butane-1R,2R,3S,4-tetraol
1-[5-(2S,3S,4-trihydroxybutyl)pyrazin-2-yl]butane-1R,2S,3S,4-tetraol
1-[5-(2R,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2R,3R,4-tetraol
1-[5-(2S,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2S,3R,4-tetraol
1-[6-(2R,3S,4-trihydroxybutyl)pyrazin-2-yl]butane-1R,2R,3S,4-tetraol
1-[6-(2R,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2R,3R,4-tetraol
1-[6-(2S,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2S,3R,4-tetraol
or a salt of such a compound with an inorganic or organic acid,
advantageously
1-[5-(2S,3S,4-trihydroxybutyl)pyrazin-2-yl]butane-1R,2S,3S,4-tetraol
1-[5-(2R,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2R,3R,4-tetraol
1-[5-(2S,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2S,3R,4-tetraol
or a salt of such a compound with an inorganic or organic acid,
and, more advantageously still, the following compound:
1-[5-(2S,3R,4-trihydroxybutyl)pyrazin-2-yl]butane-1S,2S,3R,4-tetraol
or a salt of such a compound with an inorganic or organic acid.
The stereoisomeric forms of the compounds of general formula (I) are obtained from the stereoisomeric forms of the reactants hereinbelow used by the preparation process according to the invention.
The stereoisomers of the compounds of formula (I) in which R1 represents the stereoisomeric forms of the xe2x80x94(CHOH)3xe2x80x94CH2OH chain (II), R2 represents a hydrogen atom and R3 represents the stereoisomeric forms of the xe2x80x94CH2xe2x80x94(CHOH)2xe2x80x94CH2OH chain (III), that is to say the compounds represented by the general formula (VII), can be obtained by reaction of ammonium formate with an aldose, or a mixture of 2 aldoses, of the dextrorotatory or laevorotatory series, of general formula:
CHOxe2x80x94CHOHxe2x80x94R1 xe2x80x83xe2x80x83(X) 
in which R1 has the same meaning as in the formula (I).
This reaction can preferably be carried out at a temperature of between 15xc2x0 C. and 100xc2x0 C., preferably in aqueous medium.
The aldoses are commercially available or can be obtained from:
a) commercially available aldoses:
by epimerization reactions, by application or adaptation of the methods described in Adv. Carbohydr. Chem., 13, 63, (1958), in particular in basic medium by means of a dilute aqueous sodium hydroxide solution (0.03 to 0.05%), at a temperature of between 20 and 40xc2x0 C.,
by chain-extension reactions, by application or adaptation of the methods described in xe2x80x9cThe Carbohydratesxe2x80x9d, edited by W. Pigman and D. Horton, Academic Press, New York, Volume IA, 133 (1972), and in particular by forming the cyanohydrin of the starting aldose (for example, by reaction with sodium cyanide in aqueous solution, at a temperature of between 10 and 30xc2x0 C. and in the presence of sodium hydroxide, at a pH in the region of 9), then hydrolysis of the nitrile functional group thus formed to the corresponding acid by application or adaptation of the methods described in Organic Synthesis, Volume I, page 436 and Volume III, page 85 (for example, using concentrated sulphuric acid or hydrochloric acid, in aqueous solution, at a temperature of between 20xc2x0 C. and the reflux temperature of the reaction mixture), and then reduction of the carboxylic acid functional group to the corresponding aldehyde by application or adaptation of the methods described in J. Am. Chem. Soc., 71, 122 (1949), in particular using an alkali metal borohydride (for example, sodium borohydride), in aqueous solution, at a temperature of between 20xc2x0 C. and the boiling temperature of the reaction mixture,
by chain-shortening reactions, by application or adaptation of the methods described in xe2x80x9cThe Carbohydratesxe2x80x9d, edited by W. Pigman and D. Horton, Academic Press, New York, Volume IB, 1980, page 929 or Chem. Ber., 83, 559 (1950) and in particular by converting the aldehyde functional group of the aldose to the corresponding hydroxylamine by application or adaptation of the methods described in Organic Synthesis, Volume II, page 314 (for example, using hydroxylamine hydrochloride, in aqueous solution and in the presence of a base, such as sodium carbonate, at a temperature of between 20 and 50xc2x0 C.), and then reaction with 3,4-dinitrofluorobenzene in the presence of carbon dioxide and a base, such as sodium hydrogencarbonate, in aqueous solution, and an aliphatic alcohol (for example, isopropyl alcohol), at a temperature of between 50 and 80xc2x0 C.,
b) corresponding allyl alcohols, by application or adaptation of the methods described in Science, 220, 949 (1983) and in particular using tert-butyl hydroperoxide in the presence of a titanium(IV) complex, such as the titanium(IV) isopropoxide and optically pure dialkyl tartrate (for example, diethyl tartrate) complex, followed by successive reaction with sodium thiophenolate, para-chloroperbenzoic acid in acetic anhydride, and diisopropylaluminium hydride.
The stereoisomers of the sugar of formula (X) can be those of aldoses containing 6 carbon atoms; those preferably used are D-gulose, D-galactose, D-allose, D-altrose, D-idose, D-talose, L-glucose, L-mannose, L-galactose, L-allose, L-altrose, L-idose, L-talose or L-gulose.
The stereoisomers of the compounds of formula (I) in which R1 represents the stereoisomeric forms of the xe2x80x94(CHOH)3xe2x80x94CH2OH chain (II), R2 represents the stereoisomeric forms of the xe2x80x94(CHOH)3xe2x80x94CH2OH chains (II) and R represents a hydrogen atom, that is to say compounds represented by the general formula (VIII), can be obtained by treatment, in basic medium, of an aminoaldose, or of a mixture of 2 aminoaldoses, of general formula:
CHOxe2x80x94CH (NH2)xe2x80x94R1 xe2x80x83xe2x80x83(XI) 
optionally in the form of an addition salt, such as the hydrochloride, in which R1 has the same meaning as in the general formula (I).
The reaction is preferably carried out at a temperature in the region of 20xc2x0 C. and use is preferably made of an aqueous ammonia solution and more particularly a 28% solution.
The aminoaldoses of formula (XI) are commercially available or can be prepared by application or adaptation of methods described in, for example:
(a) Methods Carbohydr. Chem., 7, 29 (1976), which consist in converting the aldehyde functional group of the corresponding aldose to a nitroethylene group using nitromethane in basic medium (for example, sodium ethoxide) and in then successively treating the product obtained with a saturated aqueous ammonia solution, at a temperature of between 20xc2x0 C. and. 30xc2x0 C., with Ba(OH)2 in aqueous solution, at a temperature of between 20xc2x0 C. and 30xc2x0 C., and finally [lacuna] dilute sulphuric acid (10 to 15%), at a temperature of between 20xc2x0 C. and 30xc2x0 C.,
(b) xe2x80x9cThe Amino Sugarxe2x80x9d, edited by R. W. Jeanloz, Academic Press, New York, 1969, page 1 or xe2x80x9cThe Carbohydratesxe2x80x9d, edited by W. Pigman and D. Horton, Academic Press, New York, Volume IB, 1980, page 664, which consist in converting the aldehyde functional group of the corresponding aldose to an imino group from a primary aromatic amine (for example aniline) and of subsequently successively reacting [lacuna] hydrocyanic acid, at a temperature of between 0xc2x0 C. and 20xc2x0 C., and [lacuna] hydrogen in the presence of palladium, in a solvent such as an ether (for example tetrahydrofuran) or an aliphatic alcohol (for example, ethanol or methanol), at a temperature of between 20xc2x0 C. and 50xc2x0 C.
The stereoisomers of the aminoaldose of formula (XI) can be those of aminoaldose comprising 6 carbon atoms; that preferably used is D-galactosamine, optionally in the form of an addition salt, such as the hydrochloride.
The stereoisomers of the compounds of formula (I) in which R1 represents the stereoisomeric forms of the xe2x80x94(CHOH)3xe2x80x94CH2OH chain (II), R2 represents the stereoisomeric forms of the xe2x80x94CH2xe2x80x94(CHOH)2xe2x80x94CH2OH chains (III) and R3 represents a hydrogen atom, that is to say compounds represented by the general formula (IX ), can be obtained
either from an aminoaldose, or from a mixture of 2 aminoaldoses, of general formula:
CHOxe2x80x94CH(NH2)xe2x80x94R1 xe2x80x83xe2x80x83(XI) 
in which R1 has the same meaning as in the general formula (I), in acidic medium and more particularly in acetic acid medium and preferably while carrying out the reaction at a temperature of between 15xc2x0 C. and 100xc2x0 C., or from a ketose, or from a mixture of 2 ketoses, of general formula:
HOCH2COxe2x80x94R1 xe2x80x83xe2x80x83(XII) 
in which R1 has the same meaning as in the general formula (I), by reaction with ammonium formate and preferably while carrying out the reaction at a temperature of between 15xc2x0 C. and 100xc2x0 C. and preferably in aqueous medium.
The ketoses of formula (XII) are commercially available or can be prepared by application or adaptation of the methods described in, for example: a) Adv. Carbohydr. Chem., 13, 63, (1958), which consist in reacting the corresponding aldose either with a base, such as calcium hydroxide, sodium hydroxide, pyridine or quinoline, or with an acid, such as sulphuric acid, in aqueous solution or in the pure phase, at a temperature of between 20 and 50xc2x0 C.,
b) Tetrahedron Asymmetry, 7(8), 2185, (1996), J. Am. Chem. Soc., 118(33), 7653 (1996), J. Org. Chem., 60(13), 4294 (1995), Tetrahedron Lett., 33(36), 5157 (1992), J. Am. Chem. Soc., 113(17), 6678 (1991), Angew. Chem., 100(5), 737, (1988), J. Org. Chem., 57, 5899 (1992), which consist, for example, in condensing either hydroxypyruvaldehyde, 1,3-dihydroxyacetone, 1,3-dihydroxyacetone monophosphate or hydroxypyruvic acid with a 2-hydroxyacetaldehyde which is substituted in the 2 position and which is optionally optically pure, optionally in the presence of an enzyme, such as a transketolase. This reaction is generally carried out in an aqueous solution, at a temperature of between 20 and 50xc2x0 C., optionally in the presence of a base (for example, sodium hydroxide), of barium chloride, of magnesium chloride or of zinc chloride. Derivatives possessing a 2-hydroxyacetaldehyde group are commercially available or can be prepared from aldoses by application or adaptation of the methods described in P. Collins and R. Ferrier, Monosaccharides, Their Chemistry and Their Roles in Natural Products, published by J. Wiley (1995), and M. Bols, Carbohydrate Building Blocks, published by J. Wiley (1996).
The stereoisomer of the aminoaldose of formula (XI) preferably used is D-galactosamine.
The stereoisomers of the compounds of formula (XII) can be those of ketoses comprising 6 carbon atoms; those preferably used are D-psicose, D-sorbose, D-tagatose, L-psicose, L-fructose, L-sorbose-or L-tagatose.
The reaction mixtures obtained by the various processes described above are treated according to conventional physical (evaporation, extraction, distillation, chromatography or crystallization, for example) or chemical (formation of salts, for example) methods.
The compounds of formula(I) can optionally be converted to addition salts with an inorganic or organic acid by the action of such an acid in an organic solvent, such as an alcohol, a ketone, an ether or a chlorinated solvent. These salts also form part of the invention.
Mention may be made, as examples of pharmaceutically acceptable salts, of the addition salts with inorganic or organic acids, such as acetate, propionate, succinate, benzoate, fumarate, maleate, oxalate, methanesulphonate, isethionate, theophyllinacetate, salicylate, methylenebis(b-oxynaphthoate), hydrochloride, sulphate, nitrate and phosphate.
The following examples more particularly illustrate the preparation process used according to the invention.